Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine.

As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.

Intramolecular addition of benzyl anion to alkyne utilizing [1,2]-phospha-Brook rearrangement under Brønsted base catalysis.

A novel reaction system for intramolecular addition of benzyl anions to alkynes was developed by utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The present reaction is a rare example of a catalytic addition reaction of an unstabilized benzyl anion under Brønsted base catalysis.

Structural change of 1-butyl-3-methylimidazolium tetrafluoroborate + water mixtures studied by infrared vibrational spectroscopy.

Mixtures of ionic liquid (IL, 1-butyl-3-methylimidazolium tetrafluoroborate, [BMIM][BF4]) and water with varying concentrations were studied by attenuated total reflection infrared absorption and Raman spectroscopy. Changes in the peak intensities and peak positions of CHx (x = 1, 2, 3) vibration modes of the cation of the IL and OH vibration modes of the water molecules were investigated. Peaks from normal-mode stretch vibrations of CH bonds belonging to the imidazolium ring of the cation did not change their positions, while those from the terminal methyl group of the butyl chain blueshifted by approximately 10 cm-1 with the addition of water. On the other hand, change in the spectral shape in the OH stretch vibration region shows hydrogen-bonding network of water molecules breaking down rapidly as the IL is added. Trends in the change of the peak positions and the peak intensities suggested qualitative change of the intermolecular structure in the [BMIM][BF4] + H2O mixture at 32 +/- 2 and 45 +/- 2 mol/L of water concentration.

The return trip is felt shorter only postdictively: A psychophysiological study of the return trip effect [corrected].

The return trip often seems shorter than the outward trip even when the distance and actual time are identical. To date, studies on the return trip effect have failed to confirm its existence in a situation that is ecologically valid in terms of environment and duration. In addition, physiological influences as part of fundamental timing mechanisms in daily activities have not been investigated in the time perception literature. The present study compared round-trip and non-round-trip conditions in an ecological situation. Time estimation in real time and postdictive estimation were used to clarify the situations where the return trip effect occurs. Autonomic nervous system activity was evaluated from the electrocardiogram using the Lorenz plot to demonstrate the relationship between time perception and physiological indices. The results suggest that the return trip effect is caused only postdictively. Electrocardiographic analysis revealed that the two experimental conditions induced different responses in the autonomic nervous system, particularly in sympathetic nervous function, and that parasympathetic function correlated with postdictive timing. To account for the main findings, the discrepancy between the two time estimates is discussed in the light of timing strategies, i.e., prospective and retrospective timing, which reflect different emphasis on attention and memory processes. Also each timing method, i.e., the verbal estimation, production or comparative judgment, has different characteristics such as the quantification of duration in time units or knowledge of the target duration, which may be responsible for the discrepancy. The relationship between postdictive time estimation and the parasympathetic nervous system is also discussed.